ORIGINAL ARTICLE Reirradiation of head and neck cancer: Long-term disease control and toxicity Wouter T C Bots, MD,1* Sven van den Bosch, MD,1 Ellen M Zwijnenburg, MD,1 Tim Dijkema, MD, PhD,1 Guido B van den Broek, MD, PhD,2 Willem L J Weijs, MD,3 Lia C G Verhoef, MD, PhD,1 Johannes H A M Kaanders, MD, PhD1 Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands, 2Department of Otorhinolaryngology Head and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands, 3Department of Oral and Maxillofacial Surgery, Radboud University Medical Center, Nijmegen, The Netherlands Accepted 29 December 2016 Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com) DOI 10.1002/hed.24733 ABSTRACT: Background The purpose of this study was to report longterm disease control and late radiation toxicity for patients reirradiated for head and neck cancer Methods We conducted a retrospective analysis of 137 patients reirradiated with a prescribed dose 45 Gy between 1986 and 2013 for a recurrent or second primary malignancy Endpoints were locoregional control, overall survival (OS), and grade 4 late complications according to European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) criteria Results Five-year locoregional control rates were 46% for patients reirradiated postoperatively versus 20% for patients who underwent reirradiation as the primary treatment (p < 05) Sixteen cases of serious (grade 4) late toxicity were seen in 11 patients (actuarial 28% at years) In patients reirradiated with intensity-modulated radiotherapy (IMRT), a borderline improved locoregional control was observed (49% vs 36%; p 07), whereas late complication rates did not differ Conclusion Reirradiation should be considered for patients with a recurrent or second primary head and neck cancer, especially postoperatively, C 2017 The Authors Head & Neck Published by Wiley Periodiif indicated V cals, Inc Head Neck 00: 000–000, 2017 INTRODUCTION such as intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT), allow better sparing of uninvolved tissue.7 A major drawback of reirradiation in the head and neck region remains the concern for severe late radiation toxicity This includes extensive fibrosis, soft tissue necrosis, osteoradionecrosis (ORN), myelopathy, and carotid artery blowout In literature, serious (European Organization for Research and Treatment of Cancer [EORTC]/Radiation Therapy Oncology Group [RTOG] grade or higher) late treatment complication rates of up to 50% are reported, although rates vary greatly because of heterogeneous study populations.8–12 This retrospective single center study includes one of the largest cohorts of patients reirradiated for head and neck tumors with a long-term follow-up The purpose of this study was to gain more insight on disease control and late radiation toxicity in both primary and postoperative reirradiation in the head and neck region This will help to determine which patients will benefit the most from reirradiation and if IMRT indeed reduces the risk of severe late toxicity Up to 40% of patients treated for head and neck cancer develop a recurrence within years after treatment.1,2 In addition, the probability of developing a second primary tumor in the head and neck area is approximately 20%, frequently associated with a history of tobacco and/or alcohol abuse.3 Traditionally, surgery is the treatment of choice for locoregional recurrences of head and neck cancer in a previously irradiated area.4,5 However, surgery is not always a feasible option because of irresectability of the tumor in advanced stages or the condition of the patient not allowing surgery Therefore, reirradiation often is the only possible alternative with curative intent Furthermore, even after surgery, reirradiation may still be indicated in patients with adverse histopathologic features, such as positive resection margins or nodal metastases with extracapsular extension.6 Over the last decade, reirradiation has gained more acceptance As a result, patients who currently develop a recurrence or a second primary malignancy are increasingly being considered for reirradiation An important reason for this trend is that highly conformal irradiation techniques, KEY WORDS: reirradiation, head and neck cancer, intensity-modulated radiotherapy (IMRT), late toxicity, disease control MATERIALS AND METHODS *Corresponding author: W T C Bots, Department of Radiation Oncology, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands E-mail: Wouter.Bots@radboudumc.nl This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited Patient selection The medical records of 167 consecutive patients who were reirradiated to the head and neck region between 1986 and 2013 for a recurrent or second primary malignancy were analyzed All patients were treated at the Radboud HEAD & NECK—DOI 10.1002/HED MONTH 2017 BOTS ET AL University Medical Center, Nijmegen, The Netherlands The date of last data collection was June 2015 Inclusion criteria were external-beam radiotherapy with a prescribed dose of at least 45 Gy in both primary treatment and retreatment, and histological proof of disease before both treatments Exclusion criteria were age